The use of genetic immunization, or immunization with DNA encoding polypeptide immunogens, to prime immune responses is viewed as a promising vaccine strategy. This technology offers potential improvements compared to other types of vaccines, such as subunit proteins complexed with adjuvants or inactivated or attenuated viral preparations. In addition to the practical advantages of simplicity of construction and modification, injection of genetic material encoding for polypeptide immunogens results in synthesis of the immunogens in the host. Thus, these immunogens are presented to the host immune system with native post-translational modifications, structure, and conformation.
In mice, several DNA vaccines have been effective at inducing long-lived antibody and cytotoxic T lymphocyte (CTL) responses and have conferred protective immunity against a number of viruses, bacteria, parasites, and tumors (1-8). Various approaches to enhance immune responses mediated by genetic immunization have been investigated. In addition to variations in dosage, route or boosting regimens, these variations include co-injection of polynucleotides encoding co-stimulatory molecules which improve immunogen presentation to lymphocytes, such as B7-1 or B7-2, or cytokines, such as GM-CSF, IL-2, IL-2, and IL-12, to create an optimal cytokine microenvironment for T cell priming (11-19). However, further enhancement of immune responses to genetic immunization is desirable for immunizing mammals, particularly humans, against immunogens such as virus- and tumor-specific immunogens.
Thus, there is a need in the art for methods of enhancing the immune responses to DNA immunogens.